Abstract
PTPN11 is closely associated with cancer progression. This study aimed to explore its prognostic potential in papillary thyroid carcinoma (PTC) and identify additional PTPN11-related prognostic genes, thereby providing novel insights for PTC treatment. Bulk and single-cell transcriptomic data from public databases were utilized to perform pan-cancer analysis for mining the oncogenic potential of PTPN11, accompanied by functional enrichment, immune infiltration, and drug molecular docking analyses. Univariate Cox regression and least absolute shrinkage and selection operator analyses were employed to screen prognostic genes and construct a risk model. Finally, single-cell level analysis was conducted to identify PTPN11-related key cells and their communication patterns. Pan-cancer analysis revealed that PTPN11 expression levels (high vs low) were significantly correlated with survival differences in PTC and other cancers (P < .05). PTPN11 was enriched in the ribosome and oxidative phosphorylation pathways and negatively correlated with CD56 bright natural killer cells (cor = -0.35, P < .05). It exhibited strong binding affinities with VX-11e, irinotecan, and dactinomycin. Eight prognostic genes (ATP2C2, OPRK1, CLSTN2, AGRP, MMP8, B3GNT4, KCNMB2, and DACT2) were screened out, and a robust risk model was established. Endothelial cells were identified as key cells; the occurrence of PTC reduced their quantity and affected the frequency/intensity of their interactions with mast cells. In conclusion, PTPN11 holds promise as a prognostic marker for PTC and is of great value for clinical management.